Is the Increased Transmissibility of SARS-CoV-2 Variants Driven by within or Outside-Host Processes?

Abstract

Understanding the factors that increase the transmissibility of the recently emerging variants of SARS-CoV-2 can aid in mitigating the COVID-19 pandemic. Enhanced transmissibility could result from genetic variations that improve how the virus operates within the host or its environmental survival. Variants with enhanced within-host behavior are either more contagious (leading infected individuals to shed more virus copies) or more infective (requiring fewer virus copies to infect). Variants with improved outside-host processes exhibit higher stability on surfaces and in the air. While previous studies focus on a specific attribute, we investigated the contribution of both within-host and outside-host processes to the overall transmission between two individuals. We used a hybrid deterministic-continuous and stochastic-jump mathematical model. The model accounts for two distinct dynamic regimes: fast-discrete actions of the individuals and slow-continuous environmental virus degradation processes. This model produces a detailed description of the transmission mechanisms, in contrast to most-viral transmission models that deal with large populations and are thus compelled to provide an overly simplified description of person-to-person transmission. We based our analysis on the available data of the Alpha, Epsilon, Delta, and Omicron variants on the household secondary attack rate (hSAR). The increased hSAR associated with the recent SARS-CoV-2 variants can only be attributed to within-host processes. Specifically, the Delta variant is more contagious, while the Alpha, Epsilon, and Omicron variants are more infective. The model also predicts that genetic variations have a minimal effect on the serial interval distribution, the distribution of the period between the symptoms’ onset in an infector–infectee pair.